Pompholyx is a vesicobullous disorder of the palms and soles. The condition is hard to treat because of the peculiarities of the affected skin, namely the thick horny layer and richness of the sweat glands. In this article, we review the available therapies, and score the treatments according to the level of evidence. The cornerstones of topical therapy are corticosteroids, although calcineurin inhibitors also seem to be effective. Topical photochemotherapy with methoxsalen (8-methoxypsoralen) is as effective as systemic photochemotherapy or high-dose UVA-1 irradiation. Systemic therapy is often necessary in bullous pompholyx. Corticosteroids are commonly used although no controlled study has been published to date. For recalcitrant cases, corticosteroids are combined with immunosuppressants. Alitretinoin has efficacy in chronic hand dermatitis including pompholyx. Another evolving treatment seems to be the intradermal injection of botulinum toxin. Radiotherapy might be an option for selected patients not responding to conventional treatment. In practice, patients benefit most from a combination of treatments.